The long-term goal of this project is to identify the virus associated with LGL leukemia. This application represents a combination of classical and cutting edge approaches led by a multi-disciplinary team whose members are internationally recognized for their individual contributions to cancer research and mammalian genomics. We propose that LGL leukemia is caused by a novel retrovirus with similarities to both HTLV and HIV. We will use classical virology methods to isolate the LGL leukemia virus. We will test the hypothesis that the LGL virus can be transmitted from infected cells to target cells and identify optimum targets for high titer virus production. We will use state-of-the-art deep sequencing combined with whole genome analytical approaches to identify LGL leukemia viral sequences. PUBLIC HEALTH RELEVANCE: This study is investigating the role of a virus in LGL leukemia development. The purpose of this study is to identify the LGL leukemia virus and to understand how it might cause leukemia. This information will make it easier to detect people who are at risk for LGL leukemia, to prevent LGL leukemia and to better treat patients who are affected by the LGL leukemia virus. It will also allow us to determine if the LGL leukemia virus is involved in other cancers and diseases with features that are similar to LGL leukemia.